Biomimetic engineering of the cardiac tissue through processing, functionalization, and biological characterization of polyester urethanes

Abstract

Three-dimensional (3D) tissue models offer new tools in the study of diseases. In the case of the engineering of cardiac muscle, a realistic goal would be the design of a scaffold able to replicate the tissue-specific architecture, mechanical properties, and chemical composition, so that it recapitulates the main functions of the tissue. This work is focused on the design and preliminary biological validation of an innovative polyester urethane (PUR) scaffold mimicking cardiac tissue properties. The porous scaffold was fabricated by thermally induced phase separation (TIPS) from poly(ε-caprolactone) diol, 1,4-butanediisocyanate, and l-lysine ethyl ester. Morphological and mechanical scaffolds characterization was accomplished by confocal microscopy, and micro-tensile and compression techniques. Scaffolds were then functionalized with fibronectin by plasma treatment, and the surface treatment was studied by x-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared spectra, and contact angle measurements. Primary rat neonatal cardiomyocytes were seeded on scaffolds, and their colonization, survival, and beating activity were analyzed for 14 days. Signal transduction pathways and apoptosis involved in cells, the structural development of the heart, and its metabolism were analyzed. PUR scaffolds showed a porous-aligned structure and mechanical properties consistent with that of the myocardial tissue. Cardiomyocytes plated on the scaffolds showed a high survival rate and a stable beating activity. Serine/threonine kinase (AKT) and extracellular signal-regulated kinases (ERK) phosphorylation was higher in cardiomyocytes cultured on the PUR scaffold compared to those on tissue culture plates. Real-time polymerase chain reaction analysis showed a significant modulation at 14 days of cardiac muscle (MYH7, prepro-ET-1), hypertrophy-specific (CTGF), and metabolism-related (SLC2a1, PFKL) genes in PUR scaffolds.

Fabrication and Plasma Modification of Nanofibrous Tissue Engineering Scaffolds

“…Interestingly, the coating of n-HA on the surface of electrospun PLLA nanofibers was also found effective for bone formation within 10 weeks after subcutaneous implantation, which was not the case when using plasma-activated PLLA scaffolds. Consequently, the authors suggested that the n-HA directly coated on the surface of nanofibers can induce ectopic bone formation in vivo in the absence of exogenous inductive agents or cells [297].…”

“…Besides plasma activation, which is by far the most commonly applied plasma-based method to nanofibrous TE scaffolds, some authors have also conducted plasma polymerization experiments on electrospun nanofibers [297][298][299][300][301]. In this case, monomer molecules in the vapor phase (typically carried by an inert gas flow) are introduced in the active plasma region.…”

Current State of the Art in Ventricle Tissue Engineering

“…The second step involves biomaterial synthesis, which entails the development of novel biomaterials that can be used to simulate mammalian extracellular matrix (ECM). A large number of biomaterials have been used in the field, to include collagen type I, fibrin, gelatin, alginate, and chitosan, to name a few (18). The third step involves coupling contractile CMs with novel biomaterials to generate functional ventricles, in other words, develop novel fabrication methods to bioengineer functional ventricles.…”

“…The notion to bioengineer cardiac patches is easy to understand as the potential applications to repair infarcted myocardium tissue are now well-established (18,19). Similarly, the utility of vascular grafts, aortic and mitral valves, and whole hearts for potential therapeutic purposes is evident and well-described (19).…”

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

“…In addition to traditional 2-dimensional (2D) in vitro systems, three-dimensional (3D) tissue models have also offered new tools in the study of cardiovascular disease recently [15]. In response to 3D conditions, the activation of ERK1/2 was observed during cardiomyogenesis, and the phosphorylation of ERK1/2 was higher compared to cells on 2D films, which provides insight into ERK1/2 pathways driving heart development [16,17]. With regard to the whole organ phenomenon in a dynamically changing neuroendocrine environment under cardiac hypertrophy and heart failure, culture-based or tissue-engineering approaches have only provided some basic physiological parameters within a largely 2D or 3D environment [18].…”